Strong inhibitory effect of medroxyprogesterone acetate (MPA) on UDP-glucuronosyltransferase (UGT) 2B7 might induce drug-drug interactions

被引：25

作者：

Huang, T. ^{[2
]}

Fang, Z. Z. ^{[3
]}

Yang, L. ^{[1
]}

机构：

[1] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China

[2] Shanghai Inst Planned Parenthood Res, Natl Populat & Family Planning Key Lab Contracept, Shanghai, Peoples R China

[3] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China

来源：

PHARMAZIE | 2010年 / 65卷 / 12期

关键词：

GLUCURONIDATION;

D O I：

10.1691/ph.2010.0671

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The aim of the present study was to investigate the inhibitory effects of medroxyprogesterone acetate (MPA) on four important UGT isoforms (UGT1A1, 1A6, 1A9 and 2B7). 4-methylumbelliferone (4-MU) was used as a nonselective substrate, and recombinant UGT isoforms were utilized as an enzyme source. The results showed that MPA exhibited inhibitory effects on UGT2B7 (IC50 = 29.3 +/- 1.5 mu M), with a negligible influence on other UGT isoforms. The results obtained from Lineweaver-Burk and Dixon plots showed that MPA competitively inhibited UGT2B7. The K-i value was calculated to be 7.2 mu M. Based on the concentration of MPA in human liver, the magnitude of in vivo drug-drug interaction (DDI) was predicted. The [1]/K-i value was calculated to be 0.31, which suggested that DDIs might occur when MPA was co-administered with drugs which mainly undergo UGT2B7-mediated metabolism.

引用

页码：919 / 921

页数：3

共 11 条

[1]

Glucuronidation of the Antiretroviral Drug Efavirenz by UGT2B7 and an in Vitro Investigation of Drug-Drug Interaction with Zidovudine [J].